Agh. Can't post over there.
I love this one! Has anyone ever tried to put people on an exercise regime before antidepressant treatment? I know that exercise raises BDNF, and I think I remember that exercise + antidepressant works better than antidepressant alone... can we boost people's BDNF and thus enhance the antidepressant efficacy? Or do the pathways get saturated?

Exercise appears to be clinically effective, but I'm not sure how much this has translated over to the clinic as a first line of treatment. I know lifestyle changes are often very difficult for people.

I was considering blogging a separate paper last night on exercise specifically, actually, but there was one graph in there that gave me pause, so I decided on this one instead.

SSRIs are always a topic of interest for me, probably because I react poorly to them in a non-traditional manner. This sort of study particularly intrigues me because it describes biological factors that may contribute to it. It makes me a bit sad that I don't have access to the clinical diagnostic equipment to run these sorts of tests. Thanks for the run down.

That item illustrates what a farce much of psychiatry is. I'll just make a few comments about some of the more ridiculous statements

1. "There’s been a lot of talk recently about how antidepressants are not particularly effective."
MY COMMENT: Well, okay, so quit using addictive drugs, and figure out what is really going on. Why are so many people today being diagnosed as depressed? Are modern conditions today worse than what our ancestors experienced? Hardly. (Although all the fake journalists and screaming wackos on hate radio and Fox News may be making susceptible people depressed.)

2. "the hypothesis that symptoms of major depression are caused by decreases in the birth of new neurons in your brain."
MY COMMENT: Neurons, really? Why? What about obvious and very real external causes for depression, like financial problems, death of a relative, family strife, personal health problems? Oh, I know why: because all of BigPharma's magic potions can't fix real problems, but they can be profitable if they can be marketed for "neurons."

3. "Long term administration of antidepressants"
MY COMMENT: Long term! What the heck? What about just fixing the problem and moving on? Oh, yeah, I forgot again -- it's all about BigPharma snagging lots of long-term victims, I mean, patients.

4. "study the non-responders, and find new drugs for them as well."
MY COMMENT: Yeah, of course, for all those people who are depressed about real problems in the real world, instead of a "neuron" problem, let's keep looking for BigPharma drugs to sell them.

All this nonsense is making me depressed. Gimme a neuron fertilizer pill.

3. I think we'd all like drugs to be free when people need them. It is not the pharmacologist's fault that antidepressants require 4-6 weeks to see symptom relief. And this isn't a lie perpetuated by pharma companies either, patients report this over and over again.

4. Would you prefer we just let people suffer?

Your comments are unhelpful, and there is no point in attacking pharma here.

They are definitely addictive in the sense of causing withdrawal symptoms. Indeed there is evidence coming out now that they may cause permanent withdrawal symptoms - i.e. permanent damage, in several percent of cases.

http://onlinelibrary.wiley.com/doi/10.1111/j.1743-6109.2007.00630.x/full
notes Finally, it is becoming increasingly clear that epigenetic changes are involved in human phenotypic expression and disease [22,23]. Antidepressants can cause quite complex changes in gene expression [24], and it is possible that some of these changes are not normalized simply by withdrawing the drugs [25]. It is not unprecedented for medications to cause persistent sexual side effects mediated by such epigenetic gene expression changes. Specifically, it has been hypothesized that persistent female sexual dysfunction caused by the oral contraceptive is caused by long-term or permanent epigenetic upregulation of steroid hormone-binding globulin expression [26]. Also, experiments with rodents have shown that chronic treatment with SSRIs at a young age results in permanently decreased sexual behavior that persists into adulthood and is similar to the cases described here [27,28].******88 At the cerebral molecular level, there are profound and permanent reductions in both the rate-limiting serotonin synthetic enzyme, tryptophan hydroxylase, and the serotonin transporter, but it is not yet known if the neurochemical situation in rodents is recapitulated in humans.*****

I think it was in the last one where the authors not that - well after the drugs had been approved - big pharma was claiming that permanent sequelae were extremely rare.... now it is starting to look like the several percent range. Serious shit.

I dig that there are some people that actually do need the drugs and it is certainly better that they use them despite the downsides, but seriously these things are being handed out like candy these days. I went to the doctor about a bone related problem and he sends me back with a prescription for murtazapine, and ssri! No actual help with the actual core problem.

Since then I have been diagnosed with severe hypogonadism, which is known to be closely linked to depression. And also there may be something up with my HPA. It is known - would be interesting to look into this further, that dysregulation of the HPA is a major factor in depression. The cortisol levels are substantially higher in depressed people, but they also respond quite differently to attempts to change the dysregulation (I think it was with a mineralcorticoid blockade... mineralcorticoids are involved in hpa system feedback).

Also many antidepressants are known to have part of their benefit by also modulating the HPA, indeed not just temporarily but permanently, although some upregulate the baseline cortisol level and some downregulate so that's a little confusing....

But anyway, it's all very well to talk about the science, but on the ground as a patient it is hard to impress over a blog how disconcerting to realize that they really are careless about how they prescribe this shit. They do it very casually. In fact a doctor just a week ago *again* prescribed me another one, trazadone, for sleep related problems. She said she didn't remember exactly how it worked, just "something with serotonin I think".

The flaws in the scientific medicine system seem to accumulate as things propagate out from science, and by the time you get to a prescription in the patient's hand it's pretty sloppy, and these are powerful drugs.....

Well, this really does depend on what you mean by "addictive". To someone like me, antidepressants are NOT addictive, because just because there are physical tolerance and withdrawal symptoms doesn't mean a person is addicted. To someone who studies addictive drugs, "addiction" involves craving for the drug, high motivation to take it, and most of all, relapse, none of which are present with antidepressants. There are many other drugs which have physical tolerance and withdrawal symptoms (for example, hypertension drugs, antipsychotics, over the counter pain relievers can cause rebound headaches), and none of these are considered addictive. I think we have different definitions here, and I really think that a new term needs to be used for drugs which have physical withdrawal symptoms but are not addictive. Side effects ARE a lot more common than previously thought, but I don't know how well a study COULD really look at permanent sequelae without a several year study, and many of the long term studies are only now coming to completion.

And believe me, the HPA axis is an increasing area of study for depression in science. There are several studies showing that the HPA axis is dysregulated in human patients with depression, and that antidepressant treatment normalizes the differences in successfully treated patients. I think I've written about this once or twice, but I haven't focused on it extensively. See

And I have several other papers in the pipeline on this. The problem is that modulating the HPA axis itself may not resolve symptoms independently, not to mention that if you're talking about side effects NOW...well, we're working on it.

I agree that prescribing practices for SSRIs can be problematic. I know many PCPs are not really "up" on the academic literature on this, and standards of care are that SSRIs are the first line of treatment. That probably needs to change, but with the DSM-V, I'm not optimistic.

greg- there's no doubt that serotonin and bone actually are related, although I think there's some controversy about how (http://www.nytimes.com/2011/05/24/health/research/24bone.html). So maybe your doctor was trying to address your core problem?
Secondly, I respect what you're saying about needing to fix some types of things in people's lives that are causing depression rather than trying to medicate all distress away. The trouble is, if you want to fix something crummy about your life, it's very hard to do so while you are already quite depressed. If you doubt this, you probably haven't experienced depression like other people. If you experienced situational glumness that doesn't in the slightest slow you down, antidepressants may not have been a good call.
However, I don't know if that is typical. I think for a typical patient, the reasoning is that the drugs provide enough of a boost that the person feels ok enough to make changes (and that CBT can assist with that in carrying them out). Or, in many cases, the drugs help people who are absolutely chronically miserable- despite notably great jobs and loving families.

Sometimes doctors are "careless" about prescribing all kinds of things, not just drugs for psychological conditions. That's mostly because the drugs are, in the grand scheme of things, pretty dang safe (i.e. they don't have to worry about "first, do no harm" with SSRIs to the degree they had to worry about it with MAOIs or Tricyclics).

Also, because doctors hate to not do things. That's not a ding on doctors, it's really a reflection that they wouldn't become doctors if they didn't want to help. But the sad truth is, we can't help lots of things that go wrong with people. For example this study (http://www.nejm.org/doi/full/10.1056/NEJMoa1101549) on malaria. I've been told the researchers had to fight ethics boards incredibly hard to get a "no bolus" control arm... and that's exactly who did the best. Basically, small children have a life-threatening condition, and the best thing you can do for them is... nothing. Not even give them an IV. It's gotta be hard to be a doctor (ok, especially in resources-limited settings in Africa).